Dulaglutide: the newest GLP-1 receptor agonist for the management of type 2 diabetes

Ann Pharmacother. 2015 Mar;49(3):351-9. doi: 10.1177/1060028014564180. Epub 2015 Jan 6.

Abstract

Objective: To review the pharmacology, pharmacokinetics, safety, and efficacy of the glucagon-like peptide-1 receptor agonist (GLP-1 RA), dulaglutide, in the treatment of type 2 diabetes mellitus (T2D).

Data sources: A PubMed search was completed to identify publications from 1947 to October 2014 using the search terms dulaglutide and LY2189265. References were reviewed to identify additional resources.

Study selection and data extraction: Articles were included if they evaluated the pharmacology, pharmacokinetics, safety, or efficacy of dulaglutide.

Data synthesis: Dulaglutide reduces both glycosylated hemoglobin (A1C) and weight by stimulating insulin secretion and suppressing glucagon in a glucose-dependent manner, delaying gastric emptying, and promoting satiety. Dulaglutide consists of 2 GLP-1 analogues that have been modified to make it a long-acting, once-weekly agent. Dulaglutide has been studied as monotherapy and in combination with metformin, glimepiride, pioglitazone, and insulin lispro. It has demonstrated superior A1C reduction compared with placebo, metformin, insulin glargine, sitagliptin, and twice-daily exenatide. It demonstrated noninferiority in A1C reduction to liraglutide. Dulaglutide changed A1C by -0.78% to -1.51%, and it changed weight by -0.35 kg to -3.03 kg. The most common adverse effects in clinical studies were nausea, vomiting, and diarrhea.

Conclusions: Dulaglutide is the fifth GLP-1 RA approved for T2D in the United States. It is an attractive option because it is dosed once-weekly, provides A1C lowering similar to liraglutide, weight reduction similar to exenatide, and has an adverse effect profile similar to exenatide and liraglutide.

Keywords: GLP-1 receptor agonist; T2D; dulaglutide.

Publication types

  • Review

MeSH terms

  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Exenatide
  • Glucagon-Like Peptide 1 / analogs & derivatives
  • Glucagon-Like Peptide 1 / therapeutic use
  • Glucagon-Like Peptide-1 Receptor
  • Glucagon-Like Peptides / analogs & derivatives*
  • Glucagon-Like Peptides / therapeutic use
  • Glycated Hemoglobin / analysis
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Immunoglobulin Fc Fragments / therapeutic use*
  • Insulin / therapeutic use
  • Liraglutide
  • Metformin / therapeutic use
  • Peptides / therapeutic use
  • Pioglitazone
  • Pyrazines / therapeutic use
  • Receptors, Glucagon / agonists*
  • Recombinant Fusion Proteins / therapeutic use*
  • Sitagliptin Phosphate
  • Thiazolidinediones / therapeutic use
  • Triazoles / therapeutic use
  • Venoms / therapeutic use

Substances

  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Immunoglobulin Fc Fragments
  • Insulin
  • Peptides
  • Pyrazines
  • Receptors, Glucagon
  • Recombinant Fusion Proteins
  • Thiazolidinediones
  • Triazoles
  • Venoms
  • Glucagon-Like Peptides
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Metformin
  • Exenatide
  • Sitagliptin Phosphate
  • dulaglutide
  • Pioglitazone